The central nervous system (CNS) plays a key role in the regulation of arterial blood pressure and an abnormality of this central neural control may result in hypertension or predispose an individual to develop hypertension in response to other factors. Much of the research on the CNS control of blood pressure has focussed on the baroreceptor reflex, but data also support a role for the CNS in determining the average blood pressure and sympathetic vasomotor drive around which the baroreceptor reflex regulates blood pressure. Although little is presently known about CNS mechanisms involved in the chronic regulation of blood pressure and sympathetic vasomotor outflow, understanding this system is essential for understanding the role of the brain in the pathogenesis of hypertension. One approach to study this system is to examine the CNS mechanisms involved in the chronic maintenance of a normal average blood pressure in animals in which the baroreceptor reflex has been eliminated by surgical destruction of the afferent nerves. Therefore, the studies described in this application are aimed at understanding the role of the CNS in the chronic regulation of blood pressure in baroreceptor denervated rats. These studies address the following hypothesis: In baroreceptor denervated rats, the brain stem (specifically the rostral ventrolateral medulla (RVLM)) generates a normal basal drive for sympathetic vasomotor outflow, thereby maintaining a normal average blood pressure. Furthermore, elevated dietary salt intake, by enhancing the excitability of RVLM neurons, will produce hypertension in baroreceptor denervated rats. Three specific aims will be addressed. [l] To determine whether the normal sympathetic vasomotor outflow in chronic baroreceptor-denervated rats derives from a restoration of normal activity in the RVLM or instead by the activation of other circuits that compensate for a chronically overactive RVLM. [21 To determine the source of regulation of the RVLM in baroreceptor denervated rats. [3] To begin to examine the mechanism by which high dietary sodium intake elicits neurogenic hypertension in baroreceptor denervated rats; we will test the hypothesis that in baroreceptor denervated rats the salt-induced increase in arterial pressure is due to an increase in the excitability of RVLM neurons. These studies will contribute to our understanding of the chronic regulation of blood pressure exerted by the brain, and therefore may provide new insight into the pathogenesis and treatment of hypertension.